DESCRIPTION: (Adapted from the application) There is accumulating evidence that oxidative stress may play a role in the pathogenesis of atherosclerosis. There is relatively little information on the molecular pathways responsible for the altered vascular redox state in this disease. The investigators have recently shown that endothelial and vascular smooth muscle cells contain a hormone sensitive NADPH/NADH oxidase that contributes to the control of the cellular redox state. In VSM cells activation of this pathway appears to be involved in hypertrophy while in endothelial cells it appears to mediate expression of adhesion molecules. The hypothesis is that NADPH/NADH oxidase may be central to the control of the redox state of vascular cells by cytokines. The investigators propose to characterize cytokine activation of the NADPH/NADH oxidase in endothelial and vascular smooth muscle cells and to determine some of the biochemical and molecular genetic mechanisms controlling oxidase activation. They also propose to examine the effects of steady and oscillatory sheer stress on this enzyme activity. The hypothesis is that sheer may exert its effects by modifying NADPH/NADH oxidase activity. Finally, they will examine the expression of vascular NADPH/NADH oxidase components in histological sections of atherosclerotic human aortas and in the aortas of hypercholesterolemic monkeys to gain insight into the pattern of expression of this oxidase and its potential role in atherosclerosis.